Background Individuals with coronary artery disease (CAD) are at higher risk of cognitive decline and dementia, in which gray matter cerebral blood flow (CBF) plays a critical role. This study investigated the effects of High Intensity Interval Training (HIIT) and HIIT plus resistance training (RT) on CBF and other health outcomes in individuals with CAD.

Methods This trial included 105 participants with CAD (age 62.1±6.6 years, 21% women) randomly assigned to HIIT+RT (n=37), HIIT (n=35) or usual care (n=33). The primary outcome was the change in global CBF from baseline to 12-week follow-up. Secondary outcomes included: region-specific CBF (hippocampus, precuneus, and anterior/posterior cingulate cortex), cognitive function (general cognition, episodic memory, processing speed, working memory and executive function/attentional control), peak oxygen uptake (VO2peak), muscular fitness (30s sit-to-stand) and body composition [weight, body mass index (BMI), and fat and muscle mass). Data were analyzed using available-case intention-to-treat constrained (baseline-adjusted) linear mixed models. Predefined subgroup analyses were conducted for age, sex, education, and baseline level of the outcome studied.

Results No significant between-group differences were observed in CBF changes in the whole sample. However, participants with lower CBF at baseline showed greater CBF increases in the HIIT group compared to both usual care (+7.1 ml/100g/min, P=0.02) and HIIT+RT (+5.53 ml/100g/min, P=0.04). No effects were observed on regional CBF or cognition. Both exercise groups improved VO2peak compared to usual care (HIIT+RT: +2.6; HIIT: +2.5 mL/kg/min, both P<0.001). Only HIIT+RT increased muscular fitness (vs usual care: +3.3; vs HIIT: +3.1 repetitions, both P<0.001), and only HIIT decreased BMI (vs usual care: -0.47; vs HIIT+RT: -0.44 kg/m2, both P≤0.03). No life-threatening events or deaths occurred during 1995 training sessions in the exercise groups, nor in the usual care group.

Conclusion Twelve weeks of HIIT+RT or HIIT did not increase CBF in the whole sample with CAD, but HIIT effectively increased CBF in those who had poorer CBF at baseline. While no cognitive benefits were observed, we found exercise-specific improvements in other clinically relevant outcomes, such as VO₂peak, muscular fitness, and BMI.

What’s new?

This study investigated the effectiveness of two high intensity interval training (HIIT)-based programs on cerebral blood flow (CBF), cognition and other clinically relevant outcomes in individuals with coronary artery disease (CAD). This is particularly important given the accelerated cognitive decline, dementia risk, and inherent poorer cardiovascular health in individuals with CAD.

This study introduces a novel exercise model by adapting the traditional 4×4 HIIT into a 3×4 format plus 2 rounds of 8 resistance exercises. The program is time-efficient (3 sessions/week of 45 minutes) and aligns with the World Health Organization recommendations, the American and European clinical guidelines for CAD management, and American College of Sports Medicine recommendations on resistance training prescription.

What are the clinical implications?

HIIT alone was effective in increasing CBF only in individuals with low levels of CBF at baseline, and in reducing BMI in the whole sample.

Both HIIT+RT and HIIT equally improved cardiorespiratory fitness, whereas the HIIT+RT additionally improved muscular fitness.

Both HIIT+RT and HIIT were safe in this population with CAD, with no major adverse events or death occurring during roughly 2000 sessions.

The authors have declared no competing interest.

NCT06214624

https://www.frontiersin.org/journals/aging-neuroscience/articles/10.3389/fnagi.2024.1437567/full

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. The Heart-Brain Project is supported with the Grants PID2020-120249RB-I00 and PID2023-148404OB-I00 funded by MCIN/AEI/10.13039/501100011033. Additional support was obtained from the Andalusian Government (Junta de Andalucia, Plan Andaluz de Investigacion, ref. P20_00124) and the CIBER de Fisiopatologia de la Obesidad y Nutricion (CIBEROBN), Instituto de Salud Carlos III, Granada, Spain. Moreover, EB has received funding from the European Union Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No. [101064851]. AT has received funding from the Junta de Andalucia, Spain, under the Postdoctoral Research Fellows (Ref. POSTDOC_21_00745). IE-C is supported by RYC2019-027287-I grant funded by MCIN/AEI/10.13039/501100011033/and ESF Investing in your future. IM-F is supported by the Spanish Ministry of Science, Innovation and Universities (JDC2022-049642-I). AC was funded by postdoctoral research grants from the Swedish Heart-Lung Foundation (grant number 20230343), the County Council of Ostergotland, Sweden (grant number RO-990967), the Swedish Society of Cardiology, and the Swedish Society of Clinical Physiology. BF-G is supported by the Spanish Ministry of Education, Culture and Sport (PID2022-137399OB-I00) funded by MCIN/AEI/10.13039/501100011033 and FSE+. MO-R, LS-A, AC-P and JF-O are supported by the Spanish Ministry of Science, Innovation and Universities (FPU22/02476, FPU21/06192, FPU21/02594 and FPU22/03052, respectively). JM is supported by the Spanish Ministry of Science, Innovation and Universities under Beatriz Galindo 2022 fellowship program (BG22/00075). JS-M is supported by the National Agency for Research and Development (ANID)/Scholarship Program/DOCTORADO BECAS CHILE/2022-(Grant no. 72220164). The sponsors or funding agencies had no role in the design and conduct of the study, in the collection, analysis, and interpretation of data, in the preparation of the manuscript, or in the review or approval of the manuscript. This work is part of a PhD thesis conducted in the Doctoral Programme in Biomedicine of the University of Granada, Granada, Spain

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The Research Ethics Board of the Andalusian Health Service (Provincial Research Ethics Committee of Granada) gave ethical approval for this work (#1776-N-21, on December 21st, 2021). All participants provided written informed consent. All research processes were conducted in accordance with the principles of the Declaration of Helsinki and the Singapore Statement on Research Integrity.

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Metadata (e.g. study protocols, data dictionaries, data processing scripts, statistical analyses plan) of the project will be open access available when the final script is ready after the peer-review process. All metadata will be hosted in the on a GitHub repository for version control and ease of reuse (https://github.com/Heart-Brain/Heart-Brain) and archived on Zenodo (https://doi.org/10.5281/zenodo.17865709) to ensure long-term preservation and to provide digital object identifiers (DOIs). The individual patient data of the Heart-Brain trial will not be made open access, due to privacy concerns and violation of the General Data Protection Regulation (due to the low number of cases in certain specific characteristics). Individual data will be available under restricted access following the "as open as possible, as closed as necessary" principle. The data files will include pseudonymized identification codes and only contain participants who provided informed consent for data sharing. The procedure for data sharing can be requested via the PI of the study (Prof. Ortega). Following this procedure, this study fully complies with the Open Science principles including FAIR data management, reproducibility, and inclusive, collaborative practices.